Johanson-Blizzard syndrome: report of a novel mutation and severe liver involvement

Am J Med Genet A. 2008 Jul 15;146A(14):1875-9. doi: 10.1002/ajmg.a.32401.

Abstract

Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive condition characterized by pathognomonic facies and a constellation of other features most notably exocrine pancreatic insufficiency, oligodontia, growth retardation, hearing loss, mental retardation, scalp defects, hypothyroidism and imperforate anus. We report on an infant with classical JBS who also has unusually severe neonatal cholestatic liver disease that progressed to liver fibrosis and portal hypertension. Sequencing of UBR1 revealed a previously unreported homozygous missense mutation in a consensus splice acceptor site (IVS12-1G > A). This report is the first to document severe liver involvement in JBS and raises the possibility that this could be a rare but genuine association.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Animals
  • Base Sequence
  • Consanguinity
  • Craniofacial Abnormalities / genetics
  • DNA / genetics
  • Disease Models, Animal
  • Exocrine Pancreatic Insufficiency / genetics
  • Female
  • Fetal Growth Retardation / genetics
  • Genes, Recessive
  • Hearing Disorders / genetics
  • Humans
  • Hypothyroidism / genetics
  • Infant
  • Infant, Newborn
  • Liver / abnormalities*
  • Liver / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Point Mutation*
  • Pregnancy
  • Syndrome
  • Ubiquitin-Protein Ligases / deficiency
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • DNA
  • UBR1 protein, human
  • UBR1 protein, mouse
  • Ubiquitin-Protein Ligases